Chemical sensor with air via

ABSTRACT

In one embodiment, a chemical sensor is described. The chemical sensor includes a chemically-sensitive field effect transistor including a floating gate conductor having an upper surface, a first opening extending through a first material and through a portion of a second material located on the first material and a second opening extending from the bottom of the first opening to the top of a liner layer located on the upper surface of the floating gate conductor.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation under 35 U.S.C. § 120 of pending U.S.application Ser. No. 15/700,630 filed Sep. 11, 2017, which applicationclaims the benefit under 35 U.S.C. § 119(e) of U.S. ProvisionalApplication No. 62/385,399 filed Sep. 9, 2016. The entire contents ofthe aforementioned applications are incorporated by reference herein.

FIELD OF THE INVENTION

The present disclosure relates to sensors for chemical analysis, and tomethods for manufacturing such sensors.

BACKGROUND

A variety of types of chemical sensors have been used in the detectionof chemical processes. One type is a chemically-sensitive field effecttransistor (chemFET). A chemFET includes a source and a drain separatedby a channel region, and a chemically sensitive area coupled to thechannel region. The operation of the chemFET is based on the modulationof channel conductance, caused by changes in charge at the sensitivearea due to a chemical reaction occurring nearby. The modulation of thechannel conductance changes the threshold voltage of the chemFET, whichcan be measured to detect or determine characteristics of the chemicalreaction. The threshold voltage may for example be measured by applyingappropriate bias voltages to the source and drain, and measuring aresulting current flowing through the chemFET. As another example, thethreshold voltage may be measured by driving a known current through thechemFET, and measuring a resulting voltage at the source or drain.

An ion-sensitive field effect transistor (ISFET) is a type of chemFETthat includes an ion-sensitive layer at the sensitive area. The presenceof ions in an analyte solution alters the surface potential at theinterface between the ion-sensitive layer and the analyte solution, dueto the protonation or deprotonation of surface charge groups caused bythe ions present in the analyte solution. The change in surfacepotential at the sensitive area of the ISFET affects the thresholdvoltage of the device, which can be measured to indicate the presenceand/or concentration of ions within the solution. Arrays of ISFETs maybe used for monitoring chemical reactions, such as DNA sequencingreactions, based on the detection of ions present, generated, or usedduring the reactions. See, for example, Rothberg et al., U.S. Ser. No.12/002,291 (now U.S. Pat. No. 7,948,015), filed Dec. 14, 2009, which isincorporated by reference herein in its entirety. More generally, largearrays of chemFETs or other types of chemical sensors may be employed todetect and measure static or dynamic amounts or concentrations of avariety of analytes (e.g. hydrogen ions, other ions, compounds, etc.) ina variety of processes. The processes may for example be biological orchemical reactions, cell or tissue cultures or monitoring neuralactivity, nucleic acid sequencing, etc.

An issue that arises in the operation of large scale chemical sensorarrays is the susceptibility of the sensor output signals to noise.Specifically, the noise affects the accuracy of the downstream signalprocessing used to determine the characteristics of the chemical orbiological process being detected by the sensors. In addition, chemicalsensor performance variation across the array results in undesirabledifferences in the sensor output signals, which further complicates thedownstream signal processing. It is therefore desirable to providedevices including low noise chemical sensors, and methods formanufacturing such devices.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure may be better understood, and its numerousfeatures and advantages made apparent to those skilled in the art byreferencing the accompanying drawings.

FIG. 1 illustrates a block diagram of components of a system for nucleicacid sequencing according to an exemplary embodiment.

FIG. 2 illustrates a cross-sectional view of a portion of the integratedcircuit device and flow cell according to an exemplary embodiment.

FIG. 3 illustrates a cross-sectional view of two representative chemicalsensors and their corresponding reaction regions according to a firstembodiment.

FIGS. 4 to 10 illustrate stages in a manufacturing process for formingan array of chemical sensors and corresponding reaction regionsaccording to a first embodiment.

The use of the same reference symbols in different drawings indicatessimilar or identical items.

DETAILED DESCRIPTION

A chemical detection device is described that includes low noisechemical sensors, such as chemically-sensitive field effect transistors(chemFETs), for detecting chemical reactions within overlying,operationally associated reaction regions.

FIG. 1 illustrates a block diagram of components of a system for nucleicacid sequencing according to an exemplary embodiment. The componentsinclude a flow cell 101 on an integrated circuit device 100, a referenceelectrode 108, a plurality of reagents 114 for sequencing, a valve block116, a wash solution 110, a valve 112, a fluidics controller 118, lines120/122/126, passages 104/109/111, a waste container 106, an arraycontroller 124, and a user interface 128. The integrated circuit device100 includes a microwell array 107 overlying a sensor array thatincludes chemical sensors as described herein. The flow cell 101includes an inlet 102, an outlet 103, and a flow chamber 105 defining aflow path for the reagents 114 over the microwell array 107. Thereference electrode 108 may be of any suitable type or shape, includinga concentric cylinder with a fluid passage or a wire inserted into alumen of passage 111. The reagents 114 may be driven through the fluidpathways, valves, and flow cell 101 by pumps, gas pressure, vacuum, orother suitable methods, and may be discarded into the waste container106 after exiting the outlet 103 of the flow cell 101. The fluidicscontroller 118 may control driving forces for the reagents 114 and theoperation of valve 112 and valve block 116 with suitable software.

The microwell array 107 includes reaction regions, also referred toherein as microwells, which are operationally associated withcorresponding chemical sensors in the sensor array. For example, eachreaction region may be coupled to a chemical sensor suitable fordetecting an analyte or reaction property of interest within thatreaction region. The microwell array 107 may be integrated in theintegrated circuit device 100, so that the microwell array 107 and thesensor array are part of a single device or chip. The flow cell 101 mayhave a variety of configurations for controlling the path and flow rateof reagents 114 over the microwell array 107. The array controller 124provides bias voltages and timing and control signals to the integratedcircuit device 100 for reading the chemical sensors of the sensor array.The array controller 124 also provides a reference bias voltage to thereference electrode 108 to bias the reagents 114 flowing over themicrowell array 107.

In operation, the array controller 124 collects and processes outputsignals from the chemical sensors of the sensor array through outputports on the integrated circuit device 100 via bus 127. The arraycontroller 124 may be a computer or other computing means. The arraycontroller 124 may include memory for storage of data and softwareapplications, a processor for accessing data and executing applications,and components that facilitate communication with the various componentsof the system in FIG. 1. In the illustrated embodiment, the arraycontroller 124 is external to the integrated circuit device 100. In somealternative embodiments, some or all of the functions performed by thearray controller 124 are carried out by a controller or other dataprocessor on the integrated circuit device 100. The values of the outputsignals from the chemical sensors indicate physical or chemicalparameters of one or more reactions taking place in the correspondingreaction regions in the microwell array 107. The user interface 128 maydisplay information about the flow cell 101 and the output signalsreceived from chemical sensors in the sensor array on the integratedcircuit device 100. The user interface 128 may also display instrumentsettings and controls, and allow a user to enter or set instrumentsettings and controls.

In some embodiments, the fluidics controller 118 may control delivery ofthe individual reagents 114 to the flow cell 101 and integrated circuitdevice 100 in a predetermined sequence, for predetermined durations, atpredetermined flow rates. The array controller 124 can then collect andanalyze the output signals of the chemical sensors indicating chemicalreactions occurring in response to the delivery of the reagents 114.During the experiment, the system may also monitor and control thetemperature of the integrated circuit device 100, so that reactions takeplace and measurements are made at a known predetermined temperature.

The system may be configured to let a single fluid or reagent contactthe reference electrode 108 throughout an entire multi-step reactionduring operation. The valve 112 may be shut to prevent any wash solution110 from flowing into passage 109 as the reagents 114 are flowing.Although the flow of wash solution may be stopped, there may still beuninterrupted fluid and electrical communication between the referenceelectrode 108, passage 109, and the microwell array 107. The distancebetween the reference electrode 108 and the junction between passages109 and 111 may be selected so that little or no amount of the reagentsflowing in passage 109 (and possibly diffusing into passage 111) reachesthe reference electrode 108. In an exemplary embodiment, the washsolution 110 may be selected as being in continuous contact with thereference electrode 108, which may be especially useful for multi-stepreactions using frequent wash steps.

FIG. 2 illustrates cross-sectional and expanded views of a portion ofthe integrated circuit device 100 and flow cell 101. The integratedcircuit device 100 includes the microwell array 107 of reaction regionsoperationally associated with sensor array 205. During operation, theflow chamber 105 of the flow cell 101 confines a reagent flow 208 ofdelivered reagents across open ends of the reaction regions in themicrowell array 107. The volume, shape, aspect ratio (such as basewidth-to-well depth ratio), and other dimensional characteristics of thereaction regions may be selected based on the nature of the reactiontaking place, as well as the reagents, byproducts, or labelingtechniques (if any) that are employed. The chemical sensors of thesensor array 205 are responsive to (and generate output signals relatedto) chemical reactions within associated reaction regions in themicrowell array 107 to detect an analyte or reaction property ofinterest. The chemical sensors of the sensor array 205 may for examplebe chemically sensitive field-effect transistors (chemFETs), such asion-sensitive field effect transistors (ISFETs).

Provided herein is a device for detecting a reaction. The reaction maybe localized to a reaction region and multiple reactions of the sametype may occur in the same reaction region. The reaction that may occurmay be a chemical reaction that results in the detection of a reactionby-product or the detection of a signal indicating a reaction. A sensormay be located in proximity to the reaction region and may detect thereaction by-product or the signal. The sensor may be a CMOS type ofsensor. In some embodiments, the sensor may detect a hydrogen ion,hydroxide ion, or the release of pyrophosphate. In some embodiments, thesensor may detect the presence of a dye molecule.

FIG. 3 illustrates a representative reaction region 301 and a chemicalsensor 314. The reaction region may be an opening such as a well,depression, or channel. Alternatively, the reaction region may be anarea where any suitable reaction takes place. A sensor array may havemillions of these chemical sensors 314 and reaction regions 301. Thechemical sensor 314 may be a chemically-sensitive field effecttransistor (chemFET), or more specifically an ion-sensitive field effecttransistor (ISFET). The chemical sensor 314 includes a floating gatestructure 318 having a sensor plate 320 coupled to a reaction region 301via an electrically conductive layer within the reaction region 301. Thefloating gate structure 318 may include multiple layers of conductivematerial within layers of dielectric material or may include a singlelayer of conductive material within a single layer of dielectricmaterial 311. The chemical sensor may include a source 321 and a drain322 located within the substrate. The source 321 and the drain 322include doped semiconductor material having a conductivity typedifferent from the conductivity type of the substrate. For example, thesource 321 and the drain 322 may comprise doped P-type semiconductormaterial, and the substrate may comprise doped N-type semiconductormaterial. A channel 323 separates the source 321 and the drain 322. Thefloating gate structure 318 overlies the channel region 323, and isseparated from the substrate by a gate dielectric 352. The gatedielectric 352 may be for example silicon dioxide. Alternatively, otherdielectrics may be used for the gate dielectric 352.

As shown in FIG. 3, the reaction region 301 is within an openingextending through dielectric materials 310 to the upper surface of thesensor plate 320. The dielectric material 310 may comprise one or morelayers of material, such as silicon dioxide or silicon nitride. Theopening also includes an upper portion 315 within the dielectricmaterial 310 and extending from the lower portion 314 to the uppersurface of the dielectric material 310. In some embodiments, the widthof the upper portion of the opening is substantially the same as thewidth of the lower portion of the reaction region. Alternatively,depending on the material(s) or etch process used to create the opening,the width of the upper portion of the opening may be greater than thewidth of the lower portion of the opening, or vice versa. The openingmay for example have a circular cross-section. Alternatively, theopening may be non-circular. For example, the cross-section may besquare, rectangular, hexagonal, or irregularly shaped. The dimensions ofthe openings, and their pitch, can vary from embodiment to embodiment.In some embodiments, the openings can have a characteristic diameter,defined as the square root of 4 times the plan view cross-sectional area(A) divided by Pi (e.g., sqrt(4*A/π)), of not greater than 5micrometers, such as not greater than 3.5 micrometers, not greater than2.0 micrometers, not greater than 1.6 micrometers, not greater than 1.0micrometers, not greater than 0.8 micrometers, not greater than 0.6micrometers, not greater than 0.4 micrometers, not greater than 0.2micrometers or even not greater than 0.1 micrometers, but, optionally,at least 0.001 micrometers, such as at least 0.01 micrometers.

In some embodiments, during manufacturing or operation of the device, athin oxide of the material of the electrically conductive material maybe grown which acts as a sensing material (e.g. an ion-sensitive sensingmaterial) for the chemical sensor. Whether an oxide is formed depends onthe conductive material, the manufacturing processes performed, and theconditions under which the device is operated. For example, in someembodiments the electrically conductive element may be titanium nitride,and titanium oxide or titanium oxynitride may be grown on the innersurface of the conductive material during manufacturing or duringexposure to solutions during use. The electrically conductive elementmay comprise one or more layers of a variety of electrically conductivematerials, such as metals or ceramics. The conductive material can befor example a metallic material or alloy thereof, or can be a ceramicmaterial, or a combination thereof. An exemplary metallic materialincludes one of aluminum, copper, nickel, titanium, silver, gold,platinum, hafnium, lanthanum, tantalum, tungsten, iridium, zirconium,palladium, or a combination thereof. An exemplary ceramic materialincludes one of titanium nitride, titanium aluminum nitride, titaniumoxynitride, tantalum nitride or a combination thereof. In somealternative embodiments, an additional conformal sensing material isdeposited on the conductive element and within the openings. The sensingmaterial may comprise one or more of a variety of different materials tofacilitate sensitivity to particular ions. For example, silicon nitrideor silicon oxynitride, as well as metal oxides such as silicon oxide,aluminum or tantalum oxides, generally provide sensitivity to hydrogenions, whereas sensing materials comprising polyvinyl chloride containingvalinomycin provide sensitivity to potassium ions. Materials sensitiveto other ions such as sodium, silver, iron, bromine, iodine, calcium,and nitrate may also be used, depending upon the embodiment.

In operation, reactants, wash solutions, and other reagents may move inand out of the reaction region 301 by a diffusion mechanism 340. Thechemical sensor 314 is responsive to (and generates an output signalrelated to) the amount of charge 324 proximate to the sensor plate 320.The presence of charge 324 in an analyte solution alters the surfacepotential at the interface between the sensor plate 320 and the analytesolution within the reaction region 301. Changes in the charge 324 causechanges in the voltage on the floating gate structure 318, which in turnchanges in the threshold voltage of the transistor. This change inthreshold voltage can be measured by measuring the current in thechannel region 323 between the source 321 and a drain 322. As a result,the chemical sensor 314 can be used directly to provide a current-basedoutput signal on an array line connected to the source 321 or drain 322,or indirectly with additional circuitry to provide a voltage-basedoutput signal.

In some embodiments, reactions carried out in the reaction region 301can be analytical reactions to identify or determine characteristics orproperties of an analyte of interest. Such reactions can generatedirectly or indirectly byproducts that affect the amount of chargeadjacent sensor plate 320 or any other materials or coatings that may beplaced on the sensor plate to increase conductivity. If such byproductsare produced in small amounts or rapidly decay or react with otherconstituents, multiple copies of the same analyte may be analyzed in thereaction region 301 at the same time in order to increase the outputsignal generated. In some embodiments, multiple copies of an analyte maybe attached to a solid phase support 312, as shown in FIG. 3, eitherbefore or after deposition into the reaction region 301. The solid phasesupport 312 may be a particle, microparticle, nanoparticle, or bead. Thesolid phase support may be solid or porous or may be a gel, or acombination thereof. The solid support may be a structure located in themiddle of the reaction region. Alternatively, the solid support may belocated at the bottom of the reaction region. For a nucleic acidanalyte, multiple, connected copies may be made by rolling circleamplification (RCA), exponential RCA, Recombinase PolymeraseAmplification (RPA), Polymerase Chain Reaction amplification (PCR),emulsion PCR amplification, or like techniques, to produce an ampliconwithout the need of a solid support.

In various exemplary embodiments, the methods, systems, and computerreadable media described herein may advantageously be used to process oranalyze data and signals obtained from electronic or charged-basednucleic acid sequencing. In electronic or charged-based sequencing (suchas, pH-based sequencing), a nucleotide incorporation event may bedetermined by detecting ions (e.g., hydrogen ions) that are generated asnatural by-products of polymerase-catalyzed nucleotide extensionreactions. This detection method may be used to sequence a sample ortemplate nucleic acid, which may be a fragment of a nucleic acidsequence of interest, for example, and which may be directly orindirectly attached as a clonal population to a solid support, such as aparticle, microparticle, bead, etc. The sample or template nucleic acidmay be operably associated to a primer and polymerase and may besubjected to repeated cycles or “flows” of deoxynucleoside triphosphate(“dNTP”) addition (which may be referred to herein as “nucleotide flows”from which nucleotide incorporations may result) and washing. The primermay be annealed to the sample or template so that the primer's 3′ endcan be extended by a polymerase whenever dNTPs complementary to the nextbase in the template are added. Then, based on the known sequence ofnucleotide flows and on measured output signals of the chemical sensorsindicative of ion concentration during each nucleotide flow, theidentity of the type, sequence and number of nucleotide(s) associatedwith a sample nucleic acid present in a reaction region coupled to achemical sensor can be determined.

Provided herein is a chemical sensor comprising a chemically-sensitivefield effect transistor (chemFET) including a floating gate conductorhaving an upper surface. At least a first material located on top of thechemFET either in proximity to or on top of the floating gate conductorand a second material located on top of the first material. The chemicalsensor has a first opening is etched into the chemical sensor and thefirst opening may extend completely through the second material and maythen extend a portion of the first material. In addition, the secondmaterial may have a second opening. The second opening may be locatedanywhere beneath the first opening but may be located in the center ofthe bottom of the first opening. The second opening extends from thebottom surface of the first opening to the top of a lining layer on themetal layer. The first material may be a dielectric material. The secondmaterial may be an oxide, such as silicon oxide. In some embodiments,the second opening of the chemical sensor may be similar in size to thefirst opening. In some embodiments, the second opening of the chemicalsensor may have a smaller area or circumference than the area orcircumference of the first opening of the chemical sensor. The width ofthe lower portion of the second opening may be substantially the same asthe width of the upper portion of the second opening or the upperportion may be wider than the lower portion of the second opening.Likewise, the width of the lower portion of the first opening may besubstantially the same as the width of the upper portion of the firstopening or alternatively, the upper portion may be wider than the lowerportion of the first opening. In some embodiments, the chemical sensormay include a biocompatible layer. The biocompatible layer may belocated on or in the bottom of the first opening but not on or in thesecond opening or the biocompatible layer may be located on or in thesecond opening but not on or in the first opening. Alternatively, thebiocompatible layer may be located on or in the first opening and on orin the second opening. The biocompatible layer may be located on theentire surface of the first, second or both first and second opening ormay be located on at least a portion of the first, second, or both firstand second opening. The biocompatible layer may be located on the bottomof the openings or on the sidewalls of the openings. Additionally, thechemical sensor may further include an electrically conductive layerover at least a portion of the first, second, or both first and secondopening. The electrically conductive layer may be located on or in thebottom of the first opening but not on or in the second opening or theelectrically conductive layer may be located on or in the second openingbut not on or in the first opening. Alternatively, the electricallyconductive layer may be located on or in the first opening and on or inthe second opening. The electrically conductive layer may be located onthe entire surface of the first, second or both first and second openingor may be located on at least a portion of the first, second, or bothfirst and second opening. The electrically conductive layer may belocated on the bottom of the openings or on the sidewalls of theopenings. The opening may be a well, such as a microwell or nanowell,but it may also be a channel, depression, indent or any other suitablestructure for a reaction region.

Further provided herein is a method for manufacturing a chemical sensor.In some embodiments, the method may include providing or forming achemically-sensitive field effect transistor including a floating gateconductor having an upper surface. A metal material is then depositedeither on top of or in proximity to the upper surface of the floatinggate conductor. On top of the metal layer, an unreactive material orliner layer is deposited. The unreactive material is one that is notremoved by during the removal of the filler material, such that themetal layer remains unaffected by and chemical clean steps. The linerlayer can be any suitable unreactive material, such as titanium nitride.A first material is then deposited on the metal layer where present onthe chemical sensor and any area not covered by metal. The methodfurther provides for forming a first opening in the first material wherethe first opening extends from the upper surface of the floating gateconductor to the top of the first material. The first material may be anoxide, such as silicon oxide. The first opening is then, according tothe method, filled with a filler material. The filler material may be ametal, such as tungsten. The filler material may be any material that isnot etched by the same etching process for forming the second opening.After the filler material is deposited in the opening, a second materialmay be deposited over the upper surface of the first material and thefiller material. The second material may be a dielectric such as siliconnitride. Further provided for in the method is forming a second openingin the structure. The second opening extends through the depth of thesecond material. In some embodiments, the second opening has a topsurface that is at the upper surface of the second material and a lowersurface that is located at the bottom of the second opening. The lowersurface may be the same as the top surface of the first material.Alternatively, the second opening may extend through the entire secondmaterial and may also extend through a portion of the first material.The extent to which the first material is etched with the secondmaterial may be a predetermined depth. The filler material however, isnot etched during this etching process and therefore may extend in thenegative space created during the second etch of the first and secondmaterial. Finally, the filler material may be removed during a separateclean-up step leaving the first opening and the second opening. Thefirst and second openings may be a well, such as a microwell, nanowell,indent, depression, or channel or combination thereof. The forming ofthe second opening may include etching the first material and the secondmaterial during the same etch step. Alternatively, the first and secondmaterials may be etched during different steps. In some embodiments, thesecond opening of the chemical sensor may be similar in size to thefirst opening. In some embodiments, the first opening of the chemicalsensor may have a smaller area or circumference than the area orcircumference of the second opening of the chemical sensor. The width ofthe lower portion of the second opening may be substantially the same asthe width of the upper portion of the second opening or the upperportion may be wider than the lower portion of the second opening.Likewise, the width of the lower portion of the first opening may besubstantially the same as the width of the upper portion of the firstopening or alternatively, the upper portion may be wider than the lowerportion of the first opening. The area of the second opening may have alarger area than the first opening. In some embodiments of the methodprovided herein, the method may further include depositing abiocompatible layer, an electrically conductive layer, or both abiocompatible and electrically conductive layer.

FIGS. 4 to 10 illustrate one embodiment of the stages in a manufacturingprocess for forming an array of chemical sensors and correspondingreaction region. FIG. 4 shows a structure 400 including a substrate 402and a metal layer 404. The substrate layer 402 may be any suitablesemiconductor material layer, for example silicon oxide. The substratelayer may include a floating gate structure as describe previouslyabove. The metal layer 404 which will be located under the air via, asshown in FIG. 10, may be deposited and patterned on the substrate layer402 using standard lithography and etch protocols. The metal layer maybe any suitable electrically conductive material including but notlimited to aluminum copper alloy, aluminum, copper, titanium, tantalum,hafnium, zinc, tungsten, gold, platinum, or silver, or any combinationthereof. The top surface (or optional liner layer) 403 of the metallayer may be any suitable material that is not removed by the subsequentair via removal process, such as titanium nitride for example, but anysuitable liner layer may be used. The metal layer 404 may be depositedover floating gates formed within the substrate 402. The floating gatesmay be multi-layer metal floating gates. Alternatively, the metal layermay be disposed over the gate dielectric or a single conductor layerover the gate dielectric.

After the metal layer 504 is deposited on the substrate, an oxide layer506 is deposited over the liner layer 503 or top surface of the metallayer 504 and the substrate layer 502 as shown in the structure 500 ofFIG. 5. The oxide layer will form the air via and may be referred to theair via oxide layer. The oxide layer may be silicon oxide or any othersuitable oxide layer. After the oxide layer 506 is deposited on theliner layer 503 of the metal layer 504 and the substrate layer 502, theoxide layer 506 is then flattened by any suitable means including, butnot limited to, chemical mechanical polish (CMP) using standarddeposition and CMP protocols.

After the oxide layer 606 is deposited on the substrate 602 and theliner layer 603 of the metal 604 of the structure 600 and flattened, theoxide layer 606 is patterned and then etched using standard via etchprotocols including but not limited to photolithographic etchingtechniques. For example, a layer of photoresist may be patterned on thedielectric material to define the locations of the openings and thenanisotropically etching the dielectric material using the patternedphotoresist as an etch mask. The anisotropic etching of the dielectricmaterial may, for example, be a dry etch process, such as a fluorinebased Reactive Ion Etching (RIE) process. The air via oxide layer isthen etched to the surface of the liner layer 603 on the metal layer 604and results in an “air via” 608 as shown in FIG. 6.

FIG. 7 shows the structure 700 including a substrate 702, liner layer703 on top of the metal layer 704, and oxide layer 706. After the airvia 608 is formed, it is then filled with a filler material 710 as shownin FIG. 7. In some embodiments, the via may be filled with tungsten,titanium, tantalum, or any other suitable filler material such that thefiller material is not etched or does not react during the subsequentmicro well etch process but is capable of being removed by post microwell etch clean up step. The filler material 710 may be deposited bysputtering, atomic layer deposition (ALD), low pressure vapor deposition(LPCVD), plasma enhanced chemical vapor deposition (PECVD), metalorganic chemical vapor deposition (MOCVD) or any other suitabledeposition technique. After filling the via with the filler material710, the filler material 710 is flattened using standard via processingprotocols, for example CMP methods. The top surface of the fillermaterial 710 may be flattened to be substantially planar with the airvia oxide layer 706. In some embodiments, more than one layer of fillermaterial may be deposited in the via or more than one type of materialmay be deposited.

After the conductive material 810 is flattened to be substantiallyplanar with the oxide layer 806 of the structure 800, a dielectricmaterial 812 may be deposited over the oxide layer 806 and theconductive material 810 as shown in FIG. 8. The dielectric material 812may be tetraethyl orthosilicate (TEOS), plasma enhanced silicon oxide(PEOX), silicon nitride, or other silicon dioxide embodiments, amorphousundoped silicon, or any suitable material. The dielectric material maybe a single layer of one type of material or a plurality of multiplelayers of materials.

The dielectric material 912 is then etched as shown in FIG. 9 to createa well 914 in the dielectric material 912. The dielectric material 912may be etched to the surface of the oxide layer 906 and the surface ofthe conductive material 910 using a suitable etching chemical.Alternatively, the microwell etch may etch into the oxide layer 906 asshown in FIG. 9 such that the conductive material 910 may extend pastthe surface of the oxide layer 906. In such an embodiment, the fillmaterial extending past the surface of the air via layer may be removedsubsequent to processing. The depth of the etch and whether the etchincludes etch of the oxide layer may be predefined.

After the etch of the dielectric material 1012 has occurred, a post etchclean out step is carried out to remove any unwanted left over polymerin the well cavity 1014. During this process, the conductive material(shown as 910 in FIG. 9) previously deposited in the via 1008 may beremoved as well as shown in FIG. 10. The clean out chemistry used inthis step should be such that the metals are removed but not any portionof the oxide layers. This clean out may be performed with fluorine orchlorine based acids, for example. The liner layer 1003 on top of themetal layer protects the metal layer 1004 from reacting during the etchprocess. After the post microwell etch clean is completed an air via1008 is located at the bottom of the well 1014. In some embodiment, anadditional layer of material may be deposited. The material may bedeposited just at the bottom of the well and may include the surfacearea of the air via or the material may be deposited on the side wallsof the well. Alternatively, the material may be deposited either fullyor at least partially on all surfaces of the well.

Provided herein is a chemical sensor comprising a chemically-sensitivefield effect transistor including a floating gate conductor having anupper surface, a first opening extending through a first material andthrough a portion of a second material, and a second opening extendingfrom the bottom of the first opening to the top of a metal layer locatedon the upper surface of the floating gate conductor. The first materialmay be a dielectric material. The second material may be an oxide, suchas silicon oxide. The second opening of the chemical sensor may have asmaller surface area than the first opening of the chemical sensor. Insome embodiments, the width of the lower portion of the second openingis substantially the same as the width of the upper portion of thesecond opening. In some embodiments, the chemical sensor may include abiocompatible layer on at least a portion of the first, second, or bothfirst and second opening. The biocompatible layer may include anysuitable biocompatible material or biological structures that may beuseful in detecting a biological event. Additionally, the chemicalsensor may further include an electrically conductive layer over atleast a portion of the first, second, or both first and second opening.The opening may be a well and the bottom of the first opening may be thesame surface as the top of the second opening.

Further provided herein is a method for manufacturing a chemical sensor,the method including forming a chemically-sensitive field effecttransistor including a floating gate conductor having an upper surface,forming a first opening in a first material extending from the uppersurface of the floating gate conductor, filling the first opening with afiller material, forming a second opening extending through a portion ofthe first material and through a second material extending, and removingthe filler material from the first opening. The filler material may betungsten. The opening may be a well. The method provided herein mayinclude forming the first opening which may further include forming anoxide layer on the floating gate conductor and etching a portion of theoxide layer to the upper surface of the floating gate conductor.Additionally, forming the second opening may include depositing adielectric on the surface of the oxide layer and the metal, etching thedielectric layer, and etching a portion of the oxide layer. The etchingprocess may include etching to the top surface, for example an oxidelayer, of the first material or may alternatively include etching pastthe top surface of the first material a predetermined depth. The etchingof a portion of the oxide layer may include etching below the topsurface of the filler material. The filler material may be a metalmaterial. The forming of the opening may include etching the firstmaterial and the second material during the same etch step.Alternatively, the first and second materials may be etched during adifferent step. The area of the second opening may have a larger areathan the first opening.

In a first aspect, a method for manufacturing a chemical sensor includesforming a chemically-sensitive field effect transistor including afloating gate conductor having an upper surface; forming a metal layeron the upper surface; forming a first opening in a first materialextending from the upper surface of the first material to the metallayer; filling the first opening with a filler material; forming asecond opening extending through a second material and a portion of thefirst material; and removing the filler material from the first opening.

In an example of the first aspect, the method further includes forming aliner layer on the metal layer prior to forming an opening in the firstmaterial. For example, the liner layer includes titanium nitride.

In another example of the first aspect and the above examples, formingthe first opening includes forming the first material over the floatinggate conductor and the metal layer, the first material comprising aninsulator; and etching a portion of the first material to the metallayer. For example, the insulator includes an oxide.

In a further example of the first aspect and the above examples, formingthe second opening includes depositing the second material on thesurface of the first material and the filler material; and etching thesecond material. For example, the method further includes etching aportion of the first material. In an example, the etching of the portionof the first material includes etching below the top surface of thefiller material. In an additional example, the second material includesa dielectric material. In another example, the dielectric materialincludes a nitride or oxide of silicon.

In an additional example of the first aspect and the above examples, theforming the second opening includes etching the first material and thesecond material during the same etch step.

In another example of the first aspect and the above examples, thefiller material is tungsten.

In a further example of the first aspect and the above examples, thesecond opening is a well.

In an additional example of the first aspect and the above examples,forming the second opening includes forming an opening having a largerarea than the area of the first opening.

In a second aspect, a chemical sensor includes a chemically-sensitivefield effect transistor including a floating gate conductor having anupper surface; a first opening extending through a first material andthrough a portion of a second material; and a second opening extendingfrom the bottom of the first opening to the top of a liner layer on ametal layer located on the upper surface of the floating gate conductor.

In an example of the second aspect, the first material is a dielectricmaterial.

In another example of the second aspect and the above examples, thesecond opening has a smaller area than the area of the first opening.

In further example of the second aspect and the above examples, a widthof the lower portion of the first opening is substantially the same as awidth of the upper portion of the first opening.

In additional example of the second aspect and the above examples, abiocompatible layer is deposited on at least a portion of the first andsecond opening.

In another example of the second aspect and the above examples, thechemical sensor further includes an electrically conductive layer.

In a further example of the second aspect and the above examples, secondopening is a well.

In an additional example of the second aspect and the above examples,the second material is an oxide. For example, the oxide is siliconoxide.

In another example of the second aspect and the above examples, the topof the second opening is the same as the bottom of the first opening.

Note that not all of the activities described above in the generaldescription or the examples are required, that a portion of a specificactivity may not be required, and that one or more further activitiesmay be performed in addition to those described. Still further, theorder in which activities are listed are not necessarily the order inwhich they are performed.

In the foregoing specification, the concepts have been described withreference to specific embodiments. However, one of ordinary skill in theart appreciates that various modifications and changes can be madewithout departing from the scope of the invention as set forth in theclaims below. Accordingly, the specification and figures are to beregarded in an illustrative rather than a restrictive sense, and allsuch modifications are intended to be included within the scope ofinvention.

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “has,” “having” or any other variation thereof, areintended to cover a non-exclusive inclusion. For example, a process,method, article, or apparatus that comprises a list of features is notnecessarily limited only to those features but may include otherfeatures not expressly listed or inherent to such process, method,article, or apparatus. Further, unless expressly stated to the contrary,“or” refers to an inclusive-or and not to an exclusive-or. For example,a condition A or B is satisfied by any one of the following: A is true(or present) and B is false (or not present), A is false (or notpresent) and B is true (or present), and both A and B are true (orpresent).

Also, the use of “a” or “an” are employed to describe elements andcomponents described herein. This is done merely for convenience and togive a general sense of the scope of the invention. This descriptionshould be read to include one or at least one and the singular alsoincludes the plural unless it is obvious that it is meant otherwise.

Benefits, other advantages, and solutions to problems have beendescribed above with regard to specific embodiments. However, thebenefits, advantages, solutions to problems, and any feature(s) that maycause any benefit, advantage, or solution to occur or become morepronounced are not to be construed as a critical, required, or essentialfeature of any or all the claims.

After reading the specification, skilled artisans will appreciate thatcertain features are, for clarity, described herein in the context ofseparate embodiments, may also be provided in combination in a singleembodiment. Conversely, various features that are, for brevity,described in the context of a single embodiment, may also be providedseparately or in any subcombination. Further, references to valuesstated in ranges include each and every value within that range.

While the present invention is disclosed by reference to the preferredembodiments and examples detailed above, it is to be understood thatthese examples are intended in an illustrative rather than in a limitingsense. It is contemplated that modifications and combinations willreadily occur to those skilled in the art, which modifications andcombinations will be within the spirit of the invention and the scope ofthe following claims.

What is claimed is:
 1. A chemical sensor comprising: achemically-sensitive field effect transistor (chemFET) including afloating gate conductor in a substrate; the floating gate conductorhaving an upper surface; a metal layer disposed over the top of theupper surface of the floating gate conductor; a liner layer disposedover the metal layer; an air via formed in a layer of a first materialdisposed over the substrate, thereby covering the metal layer and linerlayer, wherein the air via is formed through to the liner layer; and amicrowell formed in a layer of a second material disposed over the firstmaterial, wherein a bottom of the microwell is formed through to atleast a top surface of the first material.
 2. The chemical sensor ofclaim 1, wherein the first material is a dielectric material.
 3. Thechemical sensor of claim 1, wherein a biocompatible layer is depositedon at least a portion of the microwell and the air via.
 4. The chemicalsensor of claim 1, wherein the chemical sensor further includes anelectrically conductive layer.
 5. The chemical sensor of claim 1,wherein the liner layer include titanium nitride.
 6. The chemical sensorof claim 2, wherein the dielectric layer includes an oxide.
 7. Thechemical sensor of claim 1, wherein the second material includes adielectric material.
 8. The chemical sensor of claim 7, wherein thedielectric material includes a nitride or oxide of silicon.
 9. Thechemical sensor of claim 7, wherein the dielectric material includestetraethyl orthosilicate (TEOS), plasma enhanced silicon oxide (PEOX),silicon nitride, or amorphous undoped silicon.
 10. The chemical sensorof claim 7, wherein the dielectric material is a single layer of onetype of material.
 11. The chemical sensor of claim 7, wherein thedielectric material is a plurality of layers of materials.
 12. Thechemical sensor of claim 1, wherein the metal layer includes aluminumcopper alloy, aluminum, copper, titanium, hafnium, zinc, tungsten, gold,platinum, or silver, or any combination thereof.
 13. The chemical sensorof claim 1, wherein the floating gate is disposed in a layer includingan oxide of silicon.
 14. The chemical sensor of claim 2, wherein thedielectric material is an oxide layer.
 15. The chemical sensor of claim14, wherein the oxide layer is a silicon oxide layer.
 16. The chemicalsensor of claim 1, wherein the air via is in centered in the bottom ofthe microwell.
 17. The chemical sensor of claim 1, wherein the bottom ofthe microwell is etched into the first material layer.
 18. The chemicalsensor of claim 1, wherein the microwell is a reaction region.
 19. Thechemical sensor of claim 18, wherein the microwell is configured tocontain a solid support that includes multiple copies of an analyte. 20.The chemical sensor of claim 1, wherein the microwell is coupled to thechemFET.
 21. The chemical sensor of claim 1, wherein the chemFET is anISFET.